Oral infections lead to local persistent inflammation that when "uncontrolled" give rise to periodontal diseases (PD), a costly public health burden. PD is not only limited to tooth loss and associated loss of self-esteem but also impacts general health. Our recent findings indicate that resolution of inflammation is an active process and reveal an urgent need to clinically navigate this essentially uncharted terrain of infammaton-resolufion. To address this scientific opportunity and important mission in oral health, a multidisciplinary team of experts is assembled (RFA DE-04-006) in a new Specialized Center for Research (SCR) configuration that will use new technologies to elucidate the molecular map of oral resolution. Our team and overall project will provide systematic molecular analyses and insights into the integrated host resolution response with focus in oral inflammation and PD-related tissue injury. Recently, we found that human neutrophils (PMN), along with generating the many proinflammatory mediators during inflammation, also generate in exudates novel "pro- resolving" lipid mediators (LM) that possess potent anti-inflammatory and tissue protective actions, as well as activate novel anti-microbial mechanisms in mucosal epithelial cells. These ongoing studies give rise to an overarching hypothesis to be tested in four interrelated sub-projects in this SCR requiring a highly integrated approach. The SCR overall novel hypothesis addressed is: Periodontal disease (oral inflammation and tissue injury), certain microbes, surgical anesthesia, and other widely used drugs impact recently uncovered LM resolution pathways essential in host defense and homeostasis. They prolong oral inflammation by disrupting these uncharted resolution circuits. This SCR team consists of 4 sub-projects with complementary expertise and 3 scientific cores needed to map the molecular circuitry of oral resolution with a central theme of novel LM and their actions with PMN, newly uncovered anti-microbial mucosal defense mechanisms, and PMN-mediated destruction of engineered tissue matrices. Our mission's overall goal is to provide these essential molecular coordinates for swift translation to human oral health. Broad long-term objectives are a) to elucidate the map of oral resolution, b) provide molecular map(s) and coordinates to clinicians to improve treatment practices and our national preparedness and biodefense status, and c) provide the basis for new therapeutic approaches using agonists of resolution.